A study to determine whether patients who have received OMS906 in two previous studies and responded well to it, continue to tolerate it and maintain a good response
| ISRCTN | ISRCTN73211658 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN73211658 |
| IRAS number | 1008856 |
| Secondary identifying numbers | OMS906-PNH-003, IRAS 1008856, CPMS 58992 |
- Submission date
- 28/10/2023
- Registration date
- 18/12/2023
- Last edited
- 21/05/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Haematological Disorders
Plain English summary of protocol
Background and study aims
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare blood disease that causes red blood cells to break apart, releasing the haemoglobin inside. This happens because the surface of a person’s blood cells is missing a protein that protects them from the body's immune system. The release of haemoglobin causes many of the PNH symptoms like dark urine, anaemia, tiredness, difficulty swallowing and stomach pain. If left untreated, PNH can lead to serious medical complications.
This is a study to determine whether participants who have received the investigational medicine called OMS906 in two previous PNH studies and responded well to it, continue to find it safe, tolerate it well and maintain a good response to it.
OMS906 is an antibody. Antibodies work by binding to specific proteins in the body so that the harmful effect of that protein (or pathogens such as viruses) are removed. OMS906 binds to proteins involved in a specific part of the immune system. As a result, it is hoped the red blood cells in PNH patients which are missing a surface protein will not be attacked by the immune system and not break apart, thereby improving PNH symptoms, or by stopping PNH symptoms from getting worse.
Who can participate?
The study will include up to 25 participants who are over 18 years old and have participated in one of two previous OMS906 studies; one for PNH patients who had received ravulizumab previously but with only a partial response to it, and one for PNH patients who had not received previous treatment.
What does the study involve?
The study will include one evaluation visit and up to 14 treatment visits (at 8 weekly intervals) over a 2-year period.
The participants PNH symptoms will be closely monitored during the study and results from the study may be used to develop future treatments for PNH.
The study is organised and funded by Omeros Corporation a biopharmaceutical company developing PNH treatments and is being conducted at St. Jame's University Hospital in the UK and at 4 other centres in Europe.
What are the possible benefits and risks of participating?
Benefits:
Participating in the long-term extension may benefit a patient by the continued good response in terms of less anaemia, and thereby less tiredness, but this cannot be guaranteed.
Risks:
OMS906 has been given to 54 healthy volunteers. A single-dose sub-cutaneous (SC) and IV administration of OMS906 has been generally well tolerated in all volunteers. In addition, OMS906 has been given to about 25 patients in the previous PNH studies and has appeared safe and well tolerated to date. However, as with any investigational new drug or research study procedure, there may be risks that are not known that may be serious and may even cause death.
To date, the following, having been identified in animal studies and/or clinical studies, are considered as possible risks associated with giving OMS906 in humans at clinically important doses:
ALLERGIC REACTIONS: All medications can cause allergic reactions that can be mild or more serious and can result in death.
BIRTH DEFECTS (if given during pregnancy): Females who are/trying to get pregnant or are breastfeeding are excluded. Females able to become pregnant and men with a female partner able to become pregnant must use highly effective contraceptive measures during OMS906 administration and for at least 20 weeks after the last dose of OMS906.
INFECTION OR WORSENING OF EXISTING INFECTION BY CERTAIN BACTERIA: Vaccination against N. meningitidis, S. Pneumoniae and H. Influenza are required for this study. To mitigate the risk of infection, participants will be counseled and reminded of the early signs and symptoms of infection.
INFUSION/INJECTION SITE REACTIONS: These may occur such as redness, bruising, soreness or pain, or swelling in the arm or hand where the cannula is inserted.
PROCEDURAL: Risks associated with blood draws and ECG are given in the PIS.
INTERACTIONS WITH OTHER MEDICATIONS: The side effects and risks of taking OMS906 may change when it is taken with other medications, so it is very important for the participant to tell the Study Nurse about any medications (prescribed or over-the-counter) that they are taking. Participants cannot be in this study if they are taking any other unapproved medication.
The participants will be closely monitored for infections, vital signs, liver function, haematology parameters, and potential injection and infusion site reactions.
Where is the study run from?
Omeros (USA)
When is the study starting and how long is it expected to run for?
October 2023 to December 2026
Who is funding the study?
Omeros (USA)
Who is the main contact?
ctinfo@omeros.com
Contact information
Public, Scientific
201 Elliott Avenue West
Seattle
WA 98119
United States of America
| Phone | +1 206-676-5000 |
|---|---|
| ctinfo@omeros.com |
Principal Investigator
Level 3, Bexley Wing, Beckett Street
Leeds
LS9 7TF
United Kingdom
| Phone | +44 113 206 6158 |
|---|---|
| m.griffin@nhs.net |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | No participant information sheet available |
| Scientific title | An open-label study to evaluate the long-term safety, tolerability and efficacy of OMS906 in patients with paroxysmal nocturnal hemoglobinuria (PNH) |
| Study acronym | OMS906 PNH Long-term Extension Study |
| Study objectives | Primary objective: To assess long-term safety and tolerability of repeat-dose OMS906 5 mg/kg IV administration at 8-week intervals in patients with PNH. Secondary objectives: 1. To assess long-term efficacy by the effect on haemolysis and anaemia measured by haemoglobin (Hb), LDH, and red blood cell (RBC) transfusion burden 2. To assess the incidence of breakthrough haemolysis 3. To assess population pharmacokinetics (PK) and pharmacodynamics (PD) 4. To assess anti-drug antibodies (ADAs) 5. To assess the effect of OMS906 on Quality of Life, using the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale |
| Ethics approval(s) |
Approved 13/12/2023, London - Chelsea Research Ethics Committee (Research Ethics Committee (REC), London Centre, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)20 7104 8150; chelsea.rec@hra.nhs.uk), ref: 23/LO/0944 |
| Health condition(s) or problem(s) studied | Paroxysmal Nocturnal Hemoglobinuria (PNH) |
| Intervention | All patients will receive OMS906 at 5 mg/kg at intervals of every 8 weeks by intravenous infusion. Patients will be followed up at 8 weekly intervals for at least 2 years, a total of 14 visits. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Therapy |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | OMS906 |
| Primary outcome measure | The primary endpoints are safety and tolerability as assessed by AEs, vital signs, 12-lead ECGs, and clinical laboratory tests assessed from evaluation visit to end of study/termination. |
| Secondary outcome measures | 1. Efficacy as measured by: 1.1. Proportion of patients achieving Hb ≥ 12.0 g/dL assessed at 6-month intervals 1.2. Proportion of patients maintaining an increase in Hb ≥ 2 g/dL, achieved in the prior study, through the duration of the long-term extension assessed at 6-month intervals 1.3. Proportion of patients who are transfusion free at Weeks 48 and 96 1.4. Mean change from baseline in transfusion frequency from the start of the long-term extension at Weeks 48 and 96 1.5. Mean LDH change from baseline, from the start of the long-term extension, at Weeks 48 and 96 1.6. Mean change in reticulocyte count from baseline, from the start of the long-term extension, at Weeks 48 and 96 1.7. Proportion of patients experiencing clinical breakthrough hemolysis at Weeks 48 and 96 2. OMS906 population PK and PD (mature CFD) parameters assessed at day 1, treatment visits and at the end of study visit. 3. Incidence of ADAs in serum at Weeks 24, 48, 72, and 96 4. Change in FACIT-fatigue at Weeks 24, 48, 72, and 96 |
| Overall study start date | 26/10/2023 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 25 |
| Key inclusion criteria | 1. Have completed the last dosing visit of the prior OMS906 PNH study 2. Female patients of CBP must have a negative result from a highly sensitive urine pregnancy test prior to each dose of OMS906 3. Females must use highly effective birth control to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug. If a female, must be sterile (either surgically or biologically)* or at least one year postmenopausal**, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to comply with the following contraception guidelines: 3.1. Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients’ usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or 3.2. Use at least 1 of the following medically acceptable methods of birth control: hormonal methods (combined estrogen-and-progestogen-containing hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal] or progestogen only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable]), intrauterine devices, intrauterine hormone-releasing systems, or a vasectomized partner. 3.3. Defined as having had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to the Evaluation Period; or have a congenital or acquired condition that prevents childbearing. ** Defined as at least 12 months with no menses without an alternative medical cause (confirmed with follicle stimulating hormone level [FSH] in the postmenopausal range [FSH levels ≥ 40 mIU/mL during the Evaluation Period] if the patient is not using hormonal contraception or on hormonal replacement therapy). In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 4. Males must use highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug that include the following: 4.1. Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients’ usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or 4.2. Use (or have their partner use) acceptable highly effective contraception (see Criterion No. 3) during heterosexual activity. 5. Have current vaccination status for Neisseria meningitidis, Streptococcus pneumonia and Haemophilus influenza and agree to maintain vaccination throughout the study. 6. Have provided informed consent. |
| Key exclusion criteria | 1. Platelet count < 30,000/μL or absolute neutrophil count < 500 cells/μL at the start of the Evaluation Period 2. Elevation of liver function tests, defined as total bilirubin > 2 × ULN, direct bilirubin > 1.5 × ULN, and elevated transaminases, ALT or AST, > 2 × ULN unless due to PNH related hemolysis. 3. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation. 4. Patients with unresolved serious infections caused by encapsulated bacteria including H. influenzae, S. pneumoniae and N. meningitidis. 5. Pregnant, planning to become pregnant, or nursing female patients. 6. History of any significant medical, neurologic, or psychiatric disorder that in the opinion of the Investigator would make the patient unsuitable for participation in the long-term extension. 7. Unable or unwilling to comply with the requirements of the study. |
| Date of first enrolment | 15/02/2024 |
| Date of final enrolment | 31/12/2026 |
Locations
Countries of recruitment
- Germany
- Switzerland
- Ukraine
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Industry
201 Elliott Avenue West
Seattle
WA 98119
United States of America
| Phone | +1 206-676-5000 |
|---|---|
| ctinfo@omeros.com | |
| Website | http://www.omeros.com/ |
"ROR" |
https://ror.org/01r5k6556 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Omeros, Omeros Corp, OMS
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities |
| IPD sharing plan | For reasons of intellectual property the datasets generated during and/or analysed during the current study are not expected to be made available. |
Editorial Notes
21/05/2024: The public title was changed from 'A study to determine whether patients who have received OMS906 in two previous studies and responded well to it, continue to find it safe, tolerate it well and maintain a good response to it' to 'A study to determine whether patients who have received OMS906 in two previous studies and responded well to it, continue to tolerate it and maintain a good response'.
26/01/2024: The recruitment start date was changed from 29/01/2024 to 15/02/2024.
24/01/2024: Ethics approval details added. The recruitment start date was changed from 05/01/2024 to 29/01/2024.
09/01/2024: Internal review.
16/12/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 16/12/2023.
30/10/2023: Trial's existence confirmed by NHS HRA.
